Background/Objectives: Patients with relapsed/refractory (R/R) AML withFLT3mutation (FLT3mut) have a dismal prognosis.FLT3mutoffers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/RFLT3mutAML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented withFLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months,p= 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/RFLT3mutAML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.
背景/目的：携带FLT3突变的复发/难治性急性髓系白血病患者预后极差，而FLT3突变为这类患者提供了治疗靶点。两项III期临床试验已证实吉瑞替尼和奎扎替尼作为单药治疗的有效性。方法：本研究回顾性分析了西班牙27个中心在药物上市前接受吉瑞替尼或奎扎替尼单药治疗的50例R/R FLT3突变AML患者的临床特征、治疗方案及预后。其中44例接受吉瑞替尼治疗，6例接受奎扎替尼治疗。结果：患者中位年龄62.5岁，女性占52%。80%患者存在FLT3-ITD突变，治疗开始时46%为原发难治性疾病，54%为复发疾病。一线治疗中80%患者接受化疗，其中40%联合米哚妥林治疗。50%患者既往接受过FLT3抑制剂治疗，56%患者在启动吉瑞替尼/奎扎替尼治疗前接受过≥2线治疗。完全缓解率、血象未恢复的完全缓解率及部分缓解率分别为22%、18%和16%。中位总生存期和无病生存期分别为4.74个月和2.99个月。与接受≥2线治疗的患者相比，仅接受过1线治疗的患者总生存期显著延长（10.77个月 vs 4.24个月，p=0.016）。多因素分析显示未达到CR/CRi、既往治疗线数≥2、年龄及白细胞计数是总生存期的独立预后因素。最常见毒性反应包括发热性中性粒细胞减少、肝功能异常及QT间期延长。结论：在真实世界临床实践中，吉瑞替尼/奎扎替尼单药治疗是R/R FLT3突变AML患者有效且可耐受的治疗选择。尽管研究人群异质性更强，其缓解率和毒性反应发生率与III期临床试验报告结果基本一致。
肿瘤(癌症)患者之家